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Kakkalide and its metabolite irisolidone ameliorate carrageenan-induced inflammation in mice by inhibiting NF-κB pathway.

Abstract
The anti-inflammatory activities of kakkalide, a major constituent of the flower of Pueraria thunbergiana, and irisolidone, a metabolite of kakkalide produced by intestinal microflora, against carrageenan-induced inflammation in air pouches on the backs of mice and in lipopolysaccharide (LPS)-stimulated peritoneal macrophages were investigated. Kakkalide and irisolidone down-regulated the gene expression of cytokines [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)] and cyclooxygenase-2 (COX-2) and the production of pro-inflammatory cytokines, TNF-α and IL-1β, and inflammatory mediators, NO and prostaglandin E(2) (PGE(2)), in LPS-stimulated peritoneal macrophages. These agents also inhibited the phosphorylation of IκB-α and the nuclear translocation of nuclear factor-kappa B (NF-κB). Orally administered kakkalide and irisolidone significantly reduced carrageenan-induced inflammatory markers, leukocyte number, and protein amount in the exudates of the air pouch. These constituents also inhibited PGE(2) production and COX-2 inducible nitric oxide synthase, IL-1β, and TNF-α expression. These agents also inhibited NF-κB activation. The anti-inflammatory effects of irisolidone were more potent than those of kakkalide. Based on these findings, kakkalide and irisolidone may inhibit inflammatory reactions via NF-κB pathway, and irisolidone, a metabolite of kakkalide, may more potently inhibit these inflammatory reactions.
AuthorsSung-Won Min, Young-Jun Park, Dong-Hyun Kim
JournalInflammation (Inflammation) Vol. 34 Issue 5 Pg. 344-51 (Oct 2011) ISSN: 1573-2576 [Electronic] United States
PMID20686830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Flavonoids
  • Glycosides
  • Inflammation Mediators
  • Interleukin-1beta
  • Isoflavones
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • irisolidone
  • kakkalide
  • Carrageenan
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone
Topics
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Carrageenan (toxicity)
  • Cells, Cultured
  • Cyclooxygenase 2 (metabolism)
  • Dinoprostone (metabolism)
  • Flavonoids (pharmacology)
  • Glycosides (pharmacology)
  • Inflammation (chemically induced, metabolism, prevention & control)
  • Inflammation Mediators (metabolism)
  • Interleukin-1beta (metabolism)
  • Isoflavones (pharmacology)
  • Lipopolysaccharides (toxicity)
  • Macrophages, Peritoneal (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B (metabolism)
  • Nitric Oxide Synthase Type II (metabolism)
  • Signal Transduction (drug effects)
  • Tumor Necrosis Factor-alpha (metabolism)

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